The T-cell response to human cytomegalovirus (HCMV) primary infection was analyzed in 27 pregnant women during the first year after primary HCMV infection. Pregnant women with remote HCMV infection were enrolled as controls. Interferon-γ-producing T cells were readily detected at levels comparable (CD4+) or higher (CD8+) than controls, whereas the CD4+ and CD8+ lymphoproliferative response as well as IL-2 production was significantly reduced with respect to controls for at least 9 months after infection. In addition, CD45RA re-expression as well as cytotoxic T lymphocyte activity and perforin expression were the major components of the adaptive CD4+ and CD8+ T-cell immune response, while Vδ2- γδ T-cell expansion in response to HCMV infection followed kinetics similar to that of CD8+ T cells. Reduced CD45RA re-expression directly correlated with HCMV transmission to the fetus, thus providing an important prognostic parameter.